PROJECT SUMMARY Colorectal cancer (CRC) is the 2nd leading cause of cancer death in the United States. Research has consistently shown that screening reduces risks for CRC incidence and mortality. Effectiveness of screening has generally been attributed to detection and removal of precancerous polyps and curable cancers. In usual practice, routine follow up for many patients with polyps removed at baseline includes repeat surveillance colonoscopy to detect and resect additional polyps and cancer. However, the incremental benefit of surveillance colonoscopy over baseline colonoscopy with polyp removal is unclear. Indeed, prior research has not focused on effectiveness of surveillance and has not specifically determined whether a clinical strategy of systematic surveillance after baseline polypectomy reduces the risk of developing or dying from colorectal cancer, compared to no surveillance. Despite this gap in knowledge, current guidelines recommend routine surveillance colonoscopy for the majority of patients with polyps. Since colonoscopy is a burden on patients, associated with risks such as bleeding, and costly, it is imperative to establish whether surveillance reduces CRC risk. Our Specific Aims are to determine whether post polypectomy surveillance colonoscopy reduces CRC incidence (Aim 1) and mortality (Aim 2). To accomplish these aims, we will utilize a previously established cohort of over 400,000 individuals who had colonoscopy with polyp removal within the Department of Veterans Affairs (VA). Using a case-cohort design, all individuals with incident CRC identified by the VA Central Cancer Registry, all individuals with fatal CRC identified by the National Death Index, as well as a random sample of those who had polyps removed at baseline will be selected for study inclusion. We will use medical record review to determine exposure to surveillance colonoscopy and measure other factors that may influence CRC risk. Observed occurrence and timing of surveillance colonoscopy delivered will be summarized using a time- dependent exposure variable that characterizes adherence to post-polypectomy surveillance guidelines. CRC incidence, as well as CRC mortality will be compared among individuals exposed versus unexposed to surveillance colonoscopy, taking into account other factors that may influence CRC risk.